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Structures of the M1 and M2 muscarinic acetylcholine receptor/G-protein complexes.


ABSTRACT: Muscarinic acetylcholine receptors are G protein-coupled receptors that respond to acetylcholine and play important signaling roles in the nervous system. There are five muscarinic receptor subtypes (M1R to M5R), which, despite sharing a high degree of sequence identity in the transmembrane region, couple to different heterotrimeric GTP-binding proteins (G proteins) to transmit signals. M1R, M3R, and M5R couple to the Gq/ 11 family, whereas M2R and M4R couple to the Gi/ o family. Here, we present and compare the cryo-electron microscopy structures of M1R in complex with G11 and M2R in complex with GoA The M1R-G11 complex exhibits distinct features, including an extended transmembrane helix 5 and carboxyl-terminal receptor tail that interacts with G protein. Detailed analysis of these structures provides a framework for understanding the molecular determinants of G-protein coupling selectivity.

SUBMITTER: Maeda S 

PROVIDER: S-EPMC7034192 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Structures of the M1 and M2 muscarinic acetylcholine receptor/G-protein complexes.

Maeda Shoji S   Qu Qianhui Q   Robertson Michael J MJ   Skiniotis Georgios G   Kobilka Brian K BK  

Science (New York, N.Y.) 20190501 6440


Muscarinic acetylcholine receptors are G protein-coupled receptors that respond to acetylcholine and play important signaling roles in the nervous system. There are five muscarinic receptor subtypes (M1R to M5R), which, despite sharing a high degree of sequence identity in the transmembrane region, couple to different heterotrimeric GTP-binding proteins (G proteins) to transmit signals. M1R, M3R, and M5R couple to the G<sub>q/</sub> <sub>11</sub> family, whereas M2R and M4R couple to the G<sub>i  ...[more]

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